Filament material polylactide mixtures

ABSTRACT

A surgical filament produced by spinning a mixture of polylactides and additive.

This invention relates to a process for the manufacture of a polyestercomprising filament material suitable for surgical application, as suchor in woven, braided or knitted form, as well as reinforcing beads. Theinvention further relates to a synthetic surgical material that isbiocompatible with a patient and is biodegradable.

The invented process of spinning a polyester material in the presence ofa certain additive can be used in the production of highly fibrillatedsutures, which due to their fibrillation exhibit a good resorption rateand flexibility important for handling the suture and tying the knot.

Regular structurization at the fibre surface, created in the presentspinning process, and preserved in the fibre even after hot-drawing,provides to the fibre a high knot strength.

There exist a number of commercial biocompatible and biodegradablesutures based on polyglycolide (Dexon), copolymer of lactide andglycolide (Vicryl), or lactone of hydroxyethyl glycolic acid (PDS).These well known materials are convenient to handle, and have therequired rate of bioresorption. However there still exists a need fornew biocompatible and biodegradable suture materials.

As followed from literature data, polylactide fibers have already beenproduced, but the rate of degradation of these fibers is too low ascompared with that of Vicryl, Dexon or PDS sutures.

While Vicryl, Dexon and PDS sutures respectively disappear after about90, 120 and 180 days from implantation, the polylactide sutures are notresorbed until after about 8 to 17 months from implantation.

Thus although polylactide is a biocompatible, biodegradable andfiberforming polymer, the polylactide sutures have not so far foundpractical application in surgery.

It is an object of the present invention to provide sutures withadequate tensile strength, high dimensional stability and a rate ofhydrolysis comparable to those of Vicryl, Dexon or PDS sutures. It isanother object of the present invention to provide fibers which have aflexibility higher than those produced according to the standardmethods, yet having high tensile strength and modulus. It is a furtherobject of the present invention to provide sutures having a knotstrength higher than that of fibers produced by standard spinningprocedures.

These and other objects are attained by filament material produced bydry- or wet-spinning mixture comprising a polyester material and anadditive, particularly a polyurethane material. When wet-spinning acoagulant material is needed. Preferred polyester materials are poly(L-lactide), (PLLA), poly(dL-lactide) (PdLLA), and combinations thereof,having a viscosity-average molecular weight of at least about 3×10⁵ andpreferably above 5.0×10⁵ Kg/kmol, as calculated according to theformula: [n]=5.45×10⁻⁴ M_(v) ⁰.73, for a viscosity measured at 25° C. intrichlormethane.

Examples of additives other than the polyurethane material which can beused in preparing the filament material of this invention, areglycolide, lactide, camphor, benzoic acid-2-hydroxyacetate,hexamethylbenzene, 1,2-cyclohexandione and other low-molecular weightorganic compounds which are preferably soluble in trichlormethane and/ordichlormethane and ethanol, and have a melting temperature in the rangeof 40° to 180° C.

Polyurethane is a preferred additive in the spinning mixture, and assuch may be used a polyester urethane based on hexamethylenediisocyanate, 1,4-butanediol and a copolymer of lactic acid and ethyleneglycol, diethylene glycol or tetramethylene glycol; hexamethylenediisocyante, 2,4,6-tris(dimethylaminomethyl)phenol and copolymer oflactic acid and diethylene glycol, ethylene glycol., or tetramethyleneglycol, a polyester urethane based on hexamethylene diisocyanate,trimethylol propane and a copolymer of polylactic acid andtetramethylene glycol or a polyester urethane based on4,4'-diphenylmethane diisocyanate, 1,4-butanediol and polytetramethyleneadipate. The concentration of the additive in the polylactide materialmay be in the range of 1 to 45% by weight.

Filament material prepared from this kind of polylactide/additivemixture are formed by dry-spinning the polymer from a solution in a welldissolving material, in particular in dichloromethane and/ortrichloromethane at room temperature through a spinneret. The filamentmaterial obtained is thereafter, according to a particularly preferredembodiment of the process according to the invention, subjected to ahot-drawing operation applying a drawing ratio within a wide range,particularly up to about 25.

The resulting oriented filaments are strong and owing to their regularlystructurized surface form strong knots.

Owing to extensive fibrillation by virtue of using an additive, thefibres are flexible and easy to handle upon suturing or knotting andhydrolyse much faster than the standard polylactide fibers.

The invented fibers, such as the polylactide comprising fibers, exhibitvery little shrinkage when heated at 37° C. in water for 30 hours,namely, about 1 to 5 percent of their initial length. The inventedspinning process avoids degradation of the polymer during extrusion,resulting in fibers of higher tensile strength.

It is recommendable that ethylene oxide is applied for sterilization ofthe fibers, for example polylactide comprising fibers, as high-energyradiation may result in crosslinking and chain scission and somedecrease in tensile strength.

After sterilization with ethylene oxide, the sutures in sealed packages,are subjected to a vacuum of 10⁻⁴ Torr at 70° C. for 1 hour. This avoidsabsorption of sterilizing gas in the sutures.

The filaments according to the present invention have a good tensilestrength of at least, 0.4 GPa, preferably 0.7 GPA. Some have tensilestrengths as high as 0.8 to 1.0 GPa. The invented fibers are resorbed asto 50% after about 150 days, which rate of hydrolysis is comparable tothat of PDS fibers with comparable thickness and strength.

The filaments according to the invention, such as the polylactidecomprising fibers, may be woven, braided, knitted or used asmonofilaments of general surgical application, may be used asreinforcing beads for the construction of biodegradable tracheal orvascular prostheses, especially for by-pass systems. The polymericmaterial, in particular when being PLLA and/or PdLLA, which can beconverted to filaments particularly by dry-spinning may be present in aspinning solution, and this in a concentration of 10 to 40% by weight indichloromethane and/or trichloromethane, as these two solvents easilydissolve the polylactide with the above viscosity-average molecularweight of about 3×10⁵ Kg/kmol at room temperature. Spinning polylactidefibers from a solution with a concentration in the range of 10 to 40% byweight provides a monofilament of reasonable tensile strength, which isin addition regularly structurized due to the melt fracture asschematically shown in the accompanying drawing as obtained (drawingratio λ=0). Even hot-drawing at high draw ratios does not completelyremove the surface structure but results in an extension of the pitch ofthe helix structure.

The diameter of the resulting fibre will generally be in the range of0.3 to 1×10⁻⁴ m. Preferred monofilaments have a diameter of about 0.4 to1×10⁻⁴ m.

Spinnerets having orifice sizes of 0.2 to 1 mm and a length of thecapillary of 10 mm are suitable for spinning the monofilaments. Indry-spinning from dichlormethane or trichlormethane solutions, thesolution is extruded at room temperature at which the solvent evaporatesslowly. A preferred polymer concentration is 15-25, in particular about20% by weight.

The filament is extruded at a speed in the range of 0.02 to 2 mm/min.This gives no orientation to the fibre as spun. After spinning thepolylactide fibers are hot-drawn at a temperature in the range of 45° to200° C., preferably at 110°, 170°, 180° or 200° C., which temperaturedepends on the additive concentration in the polymer and the meltingtemperature of the additive.

The draw ratio λ may be up to 25, preferably 14 to 18. Take-up speed maybe in the range of 0.2 to 1 cm.sec⁻¹ with a strain rate in the range of10⁻³ sec.

The hot-drawing of fibers may be carried out in an electric tube-furnacewith a length of 60 cm under a dry, oxygen-free atmosphere. Hot-drawingat temperatures above 120° C. may reduce the molecular weight of thestarting polymer by 1-2 percent.

The filament can be colored by adding an inert material, e.g. CosmeticViolet No. 2, to the solvent before preparation of the spinningsolution.

The invention is illustrated in and by the following examples:

EXAMPLE I

Filaments with a regularly structurized surface and having a diameter of0.44×10⁻⁴ m, a tensile strength of 1 GPa, a modulus of 12 GPa, astrength of square knot of 0.6 GPa and an elongation at break of 18%were prepared by spinning poly (L-lactide) from a 20 wt % solution intrichloromethane at room temperature.

The poly(L-lactide) had a viscosity-average molecular weight of 6.0×10⁵.The fibre as spun was hot-drawn at 200° C. to a draw ratio of 20.

EXAMPLE II

Filaments with a regularly structurized surface and having a diameter of0.6×10⁻⁴ m, a tensile strength of 0.8 GPa, a modulus of 9 GPa, astrength of a square knot of 0.5 GPa and an elongation at break of 17%were prepared by spinning poly(L-lactide) which contained 10% by weightof camphor, from a 20 wt % solution in trichloromethane at roomtemperature. The poly(L-lactide) had a viscosity-average molecularweight of 6.0×10⁵. The fibre was drawn at 180° C. to a draw ratio of 4.

After hot-drawing the filaments were extracted in ethanol for 4 hours.No additive was present in the fibre after extraction. The filamentsobtained turned out to have a highly fibrillated structure.

EXAMPLE III

Filaments with a regularly structurized surface and having a diameter of0.7×10⁻⁴ m, a tensile strength of 0.65 GPa, a modulus of 8 GPa, astrength of a square knot of 0.45 G and an elongation at break of 19%were prepared by spinning poly(L-lactide) containing 5% be weight ofpolyester urethane from an 18 wt % solution in an hydroustrichlormethane. The poly(L-lactide) had a viscosity-average molecularweight of 4.0×10⁵. The fibre was drawn at 150° C. to a draw ratio of 24.The poly(L-lactide)/polyester urethane monofilament so obtained has ahighly fibrillated structure.

EXAMPLE IV

Highly fibrillated filaments having a diameter of 0.6×10⁻⁴ m, a tensilestrength at break of 0.7 GPa were kept in water at 37° C. for 10 to 200days. After about 150 days the filaments were hydrolysed as to 50%. Thisrate of hydrolysis is comparable to that of PDS filaments of similarstrength and thickness.

We claim:
 1. Filament material produced by the process involving dry orwet-spinning a mixture comprising a polyester material and an additiveselected from the group consisting of non-reactive polyurethane,glycolide, lactide, camphor, benzoic acid-2-hydroxyacetate,hexamethylbenzene, 1,2-cyclohexandione, and other low molecular weightorganic compounds having melting temperatures in the range of 40° to180° C. and which are soluble in trichloromethane, dichloromethane,ethanol and mixtures thereof, and mixtures of the foregoing members ofthe group.
 2. Filament material produced by a process according to claim1, characterized in that the filament is prepared by dry-spinning, atroom temperature, a solution in which the poly-ester ispoly-(L-lactide). PLLA, and/or poly(DL-lactide), PDLLA, in aconcentration in the range of 5-70% by weight in the presence of thepolyurethane which is a biodegradable polyester urethane material. 3.Synthetic surgical filament produced by spinning a mixture comprised ofa polyester in predominant amount by weight, the polyester having aviscosity-average molecular weight of at least about 3×10⁵ kg/kmol ascalculated according to the formula [n]=5.45×10⁻⁴ M_(y) ⁰.73, for aviscosity measured at 25° C. in trichloromethane, and an additive inlessor amount by weight, the additive being selected from the groupconsisting of polyurethanes, glycolide, lactide, camphor, benzoicacid-2-hydroxyacetate, hexamethylbenzene, 1,2-cyclohexandione, and otherlow molecular weight organic compounds having melting temperatures inthe range of 40°-180° C. and which are soluble in trichloromethane,dichloromethane, ethanol and mixtures thereof, and mixtures of theforegoing members of the group.
 4. The filament of claim 3 wherein thepolyester is a polylactide and the additive in the mixture ranges inamount from about 1 to 45% by weight.
 5. The filament of claim 4 whereinthe additive is a polyurethane.
 6. The filament of claim 4 wherein thepolylactide is poly(L-lactide) or poly(DL-lactide).
 7. Articles formedfrom the filament of claim
 1. 8. The filament of claim 3 having adiameter of about 0.3 to 1×10⁻⁴ m. and having a tensile strength of atleast about 0.4 Gpa.
 9. The filament of claim 3 resulting fromextraction of the additive subsequent to spinning.
 10. The filament ofclaim 9 wherein the additive is camphor.